The clinical course of cocaine abuse has been characterized as progressing though a number of temporal stages that advance from initial experimentation to addiction. This clinical course is paralleled by changes in the neurobiological response to cocaine, as well as residual changes in structure and function that can persist despite long periods of abstinence. The purpose of this project is to expand our understanding of the neuroadaptations accompanying chronic cocaine use, especially those critical for the expression of craving triggered by environmental and internal stimuli associated with drug availability. We will use neuroimaging methods designed to evaluate the entire brain simultaneously in order to evaluate the influence of cocaine exposure across a range of brain targets that may be critical to these behavioral changes. This project makes use of both rodent and non-human primate models of cocaine self-administration. The following questions will be addressed: 1) What is the temporal course of the development of the changes in functional activity that accompany the presentation of cocaine-predictive stimuli as a factor of duration of cocaine exposure, length of abstinence and pattern of drug administration? 2) What is the anatomical distribution of changes in functional activity within the limbic and neo-cortices that accompany the presentation of cocaine-predictive cues after long term self-administration? These studies will employ non-human primates because of the close homology of primate cortex with humans. 3) How do changes in the effects of cocaine-predictive cues on functional activity develop over the course of self-administration experience? These studies will utilize non-invasive imaging with positron emission tomography to assess rates of glucose utilization repeatedly in the same animal. This approach will permit the establishment of the temporal course of functional changes in the same animal at a number of time points. Because we will be using a within subjects design, it will also be possible to examine the time course in each individual animal, thus permitting an evaluation of individual differences in the response to chronic cocaine exposure. In short, the goal of these studies is to characterize the sites of changes in functional activity that result from chronic cocaine exposure investigating the factors important for the initiation and progression of these changes over the course of cocaine self-administration experience. These data will provide a clearer picture of the neuroadaptations that can influence behavior days, weeks or even years after abstinence.